Age-related macular degeneration is a major blinding disease of the retina whose incidence among the elderly is steadily growing. No fully preventive therapy is currently available. Animal models for this disease have been instrumental in delineating some of the inductive mechanisms for AMD. Studies on other age-related disorders, such as Alzheimers disease and atheroscleroisis, and the diabetic retina have provided important clues for elucidating common mechanisms leading to factors involved in the aging retina and AMD. The S 100B transgenic mouse was previously generated to study the role of S 100B in Alzheimers. Upon examination, this mouse shows intense staining for S 100B in the RPE and appears to exhibit most of the features of the well-characterized AMD pathology arising from RPE and choroid perturbations. Full characterization (and comparison to AMD) of the progression of this phenotype will be performed, utilizing histochemical and ultrastructural methods at various timepoints, in order to document the features exhibited by this transgenic mouse line. Additionally, the transgenic retina will be assayed for S 100B cell specific expression utilizing in situ analysis, since S 100B staining normally does not occur in the RPE. Furthermore, the specific mechanism whereby S 100B transgenics may be inducing this phenotype is intriguing based on the known role of S 100B in Alzheimers disease and its only known receptor, RAGE. Based on concentration, S100B can induce both cytokine and cytotoxic RAGEmediated effects in the CNS. The RAGE receptor is a known AGE receptor, mechanistically implicated in all aging disorders, including AMD. S100B overexpression and the induced phenotype implicate the RAGE receptor for AGE and S 100B in cells contributing to the supportive tissues of the retina. This is a completely new finding which would have important consequences for research in this area. This study would assess the possible expression and known upregulation of RAGE in response to (S100B) ligand using in situ techniques on retinal sections as well as northern and western blotting from isolated RPE cells from S100B transgenics. Additional analyses of alternative receptors, known to mediate AGE ligand responsiveness in aging tissues and the diabetic retina, will be assessed in the retina as well. In summary, the retinal pathology discovered in the S 100B transgenic mice strongly suggest that these mice can be used as an additional animal model for AMD, and mechanistically, could implicate a new target, previously unknown, which may have therapeutic implications.